PROJECT SUMMARY Each year, traumatic injuries affect millions of Americans, resulting in $671 billion in healthcare costs and lost productivity. They are also the leading cause of death before age 47 and of years of potential life lost before age 75. In addition to societal costs, symptoms, such as pain, sleep disturbance, anxiety, depression, and stress related disorders are highly prevalent following traumatic orthopaedic injuries (TOI) and may contribute to negative long-term health outcomes. Identifying symptom cluster profiles following TOI may lead to recognizing those at highest risk for negative outcomes. Although the mechanisms for symptom cluster profiles are not completely known, they may share a common etiology. Using a theoretical framework created by incorporating the National Institutes of Health Symptom Science Model and the Theory of Unpleasant Symptoms, the proposed study will utilize a cross- sectional design to describe membership in symptom cluster profiles, examine the associations between demographic and clinical factors and membership in symptom cluster profiles, and measure the extent to which serum brain-derived neurotrophic factor (BDNF) and the val66met single nucleotide polymorphism (rs6265) of the BDNF gene are associated with membership in symptom cluster profiles among a diverse sample of TOI survivors recruited within the first 24 hours of their injury in a large, urban level one trauma center. Latent profile analysis with multinomial logistic regression will be used to describe group membership in the symptom cluster profiles and their associations with demographic and clinical factors and biomarker data. The aims of this study are to 1) describe TOI survivors' membership in symptom cluster profiles, indicated by pain, sleep disturbance, and symptoms of anxiety, depression, and stress related disorders, immediately following a TOI; and 2) examine associations between demographic and clinical factors and symptom cluster profile membership among TOI survivors. 3) test the hypothesis that low serum concentrations of BDNF are associated with membership among symptom cluster profiles following TOI; and 4) test the hypothesis that the presence of the val66met SNP on one or both alleles of the BDNF gene is associated membership among symptom cluster profiles following TOI. The results of this study will provide essential preliminary data to support future studies examining self- and symptom management following TOI. The training plan includes specific experiences designed to promote extensive knowledge of the biobehavioral responses of individuals following TOI, and the screening and management of post-injury symptoms. Aligned with the NINR's strategic plan to promote precision health through research of the role of biomarkers in symptom science, the proposed work will provide an essential foundation for a career in nursing research focused on investigating biobehavioral mechanisms of, and interventions for, symptom cluster profiles in TOI survivors.